Myocardin-related transcription factor A is up-regulated by 17β-estradiol and promotes migration of MCF-7 breast cancer cells via transactivation of MYL9 and CYR61

Many lines of evidence have suggested that estrogen plays important roles not only in the initiation and proliferation of breast cancer, but also in cancer metastasis. However, the mechanistic basis of the latter events is poorly under- stood. In addition, recent studies have suggested that myo- cardin-related transcription factor A （MRTF-A） might be related to cancer metastasis. However, as reports are contradictory, certain of its roles still remain confusing. In the present study, we showed that excessive 17β-estradiol could promote the migration of MCF-7 breast cancer cells and up-regulate the expression of MRTF-A, myosin regula- tory light chain 9 （MYL9）, and cysteine-rich angiogenic inducer 61 （CYR61）. Overexpression of MRTF-A signifi- cantly promoted the migration of MCF-7 cells through its transactivation effects on MYL9 and CYR61 genes, while RNA interference-mediated knockdown of MRTF-A strong- ly inhibited transcription and expression of the target genes and reduced the migration ability of MCF-7 ceils. These results provided novel evidence supporting the metastasis- promoting functions of MRTF-A, and implied that MRTF-A might be a switch for the estrogen pathway to change its pro- liferation-promoting roles into migration-stimulating roles in breast cancer.